A novel nanotopography-based approach for reshaping nuclear morphology and gene transcription

The cell nucleus functions as the control center of the cell and plays a critical role in how cells respond to physical forces from their surrounding environment. However, our understanding of these responses remains incomplete due to a lack of tools to manipulate cells and their nuclei. To address this challenge, we are developing groundbreaking nanostructured surfaces. By placing cells on these surfaces, we can deliberately deform and alter the geometry of the cell nucleus, enabling us to map how specific genes respond to controlled mechanical stimuli. Advances in nanotechnology, experimental methods, and computational tools have made it possible to explore these processes with greater precision and detail than ever before. This research is highly significant, as it may pave the way for improved diagnostics and treatments for diseases like cancer, where dysfunctional mechanical responses in cells play a crucial role.

The cell and its nucleus constantly responds and adapts to external mechanical cues. Alterations in nuclear morphology as well as in the state of DNA condensation impact cell homeostasis, differentiation and pathogenesis. Indeed, alterations in nuclear morphologies have been considered a hallmark of cancer for decades. However, tools for inducing controlled nuclear deformations and for measuring cell and nuclear response are lacking. This severely hampers our ability to properly understand and predict how cells respond to mechanical changes in their surroundings. In this project, we propose the development and implementation of novel nanostructured surfaces to induce controlled nuclear deformation, and subsequently read out nuclear effects on DNA condensation and gene expression. This is now becoming possible due to recent progress in nanofabrication coupled with cutting edge experimental and computational tools developed by us and others.